The long-term goal is to define the way in which the sex hormones modulate the secretory immune system present in mucosal tissues. The approach presented, which uses the rat uterus as a model system, builds on recent observations obtained by the applicant demonstrating that the appearance of IgA and IgG during the estrous cycle occur in response to estrogen. The immediate objective is to search for direct evidence that 1) estrogen regulates the presence of immunoglobulins; and 2) that uterine cells are the source of those immunoglobulins present in uterine secretions. Our working hypothesis is that hormones regulate a) lymphocyte movement into the uterus, b) the synthesis of immunoglobulins by a resident population of lymphocytes, or c) the transport of IgA and/or IgG from the endometrium into uterine secretions. Uterine immune responsiveness will also be considered from the standpoint of alterations in immunoglobulins brought about by estrogen administration for short vs. long (chronic) periods of time. In all cases, immunoglobulin levels will be quantitatively investigated by using antisera that are specific for rat secretory and serum immunoglobulins. In order to determine whether the sex hormones influence that local immune systems of other mucosal tissues, similar studies in oviduct, intestine and lung secretions will be investigated by comparing immunoglobulin presence and stage of the estrous cycle. In a separate collaborative project, the role of sex hormones in the control of immunoglobulin synthesis by B-lymphocytes prepared from spleen, lymph node and Peyer's patches will also be studied. Lastly, studies are proposed to determine whether there is a relationship between the actions of estrogens on the immune system and the role of estrogens in the expression of gynecological and liver tumors.